A Phase Ib Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer
Primary Purpose
Metastatic Colorectal Cancer
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Sevacizumab
Irinotecan
5-FU
Leucovorin
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- Histological/cytological confirmed unresectable metastatic colorectal cancer patients who have failed first-line oxaliplatin-based chemotherapy
- At least one measurable lesion (according to RECIST 1.1 )
- At least 4 weeks from the last chemotherapy. If patients received anti-tumor biological products, at least four t1/2 of washout period is needed
- Toxicity from previous treatment has to restore to ≤ grade 1 (NCI CTC4.0)
- ECOG performance status 0-1
- Life expectancy ≥ 3 months
- Adequate hematologic function: ANC ≥ 1.5 × 10^9 /L, HB ≥ 90 g /L (blood transfusion allowed), PLT ≥ 100 ×10^9 /L; Adequate hepatic function: ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN (patients with liver metastases ALT ≤ 5 × ULN, AST ≤ 5 × ULN); Adequate renal function: creatinine ≤ 1 × ULN; Coagulation function: INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN
- Patients of childbearing potential (male and female) must agree to use reliable methods of contraception until at least 12 weeks after the last dose
- Patients signed written inform consent
- Willingness and capability to communicate with investigators and to comply with protocol requirements
Exclusion Criteria:
- HCV, TP or HIV antibody positive
- Previously received anti-VEGF protein drugs, such as Bevacizumab,Sevacizumab
- Previously treated with irinotecan
- History of dihydropyrimidine dehydrogenase deficiency
- Patients with alcohol or drug dependence
- Participation in other clinical trials within 4 weeks before enrollment
- Active or chronic hepatitis B infection with HBV DNA > 1.0 * 10^3 IU/mL
- Serious infection requiring intravenous antibiotic therapy
- Symptomatic brain metastases
- Patients with proteinuria at screening (urine protein ≥ 1+)
- History of abdominal fistula, gastrointestinal perforation, abdominal abscess within 6 months prior to enrollment
- History of intestinal obstruction, inflammatory bowel disease, or other intestinal diseases with chronic diarrhea as the major symptom
- Serious non-healing wounds, ulcers or fractures
- Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to enrollment
- Active bleeding within 3 months prior to enrollment
- Bleeding diathesis or coagulation disorder
- History of arterial or venous thrombosis
- History of myocardial infarction or stroke within 6 months prior to enrollment
- Unstable angina, congestive heart failure, New York Heart Association (NYHA) class II heart failure, uncontrollable arrhythmia, uncontrolled hypertension
- Expected to receive surgery during the study or within 1 month after the last dose
- The investigators consider the patients are not suitable for this trial
- Pregnant and lactating women
- Known allergies to any excipient in the study drug
- Patients can not complete this study for any other reason
Sites / Locations
- The First Bethune Hospital of Jilin UniversityRecruiting
- Fudan University Shanghai Cancer CenterRecruiting
- The First Hospital of Zhejiang ProvinceRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sevacizumab+FOLFIRI
Arm Description
Two weeks as one cycle. Cycle 1: FOLFIRI on day1-2, Sevacizumab on day3; Cycle 2 and after: Sevacizumab on day 1, and then FOLFIRI on day1-2
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD)
Secondary Outcome Measures
Adverse Events (NCI-CTC 4.0)
Plasma pharmacokinetics (PK) parameters for Sevacizumab
Plasma pharmacokinetics (PK) parameters (Cmax, Tmax, AUC, T1/2) for Irinotecan and its major metabolite SN-38
Plasma pharmacokinetics (PK) parameters for 5-FU
Potential biomarkers, including VEGF and ADA
Objective Response Rate (ORR)
Disease Control Rate (DCR)
Progression Free Survival (PFS)
Overall Survival (OS)
Full Information
NCT ID
NCT02453464
First Posted
May 19, 2015
Last Updated
April 19, 2016
Sponsor
Jiangsu Simcere Pharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02453464
Brief Title
A Phase Ib Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer
Official Title
A Phase Ib, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody(Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Unknown status
Study Start Date
August 2015 (undefined)
Primary Completion Date
December 2016 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu Simcere Pharmaceutical Co., Ltd.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in combination with FOLFIRI in patients with previously treated metastatic colorectal cancer. This study includes two stages. Stage 1 is the dose-escalation stage. Once the maximum tolerated dose (MTD) of Sevacizumab has been established, additional patients will be enrolled in the cohort-expansion stage (Stage 2).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sevacizumab+FOLFIRI
Arm Type
Experimental
Arm Description
Two weeks as one cycle. Cycle 1: FOLFIRI on day1-2, Sevacizumab on day3; Cycle 2 and after: Sevacizumab on day 1, and then FOLFIRI on day1-2
Intervention Type
Drug
Intervention Name(s)
Sevacizumab
Intervention Description
escalating doses of Sevacizumab : 3mg/kg,4mg/kg,5mg/kg
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Irinotecan: IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
Intervention Type
Drug
Intervention Name(s)
5-FU
Intervention Description
5-FU: IV solution, IV bolus over 2-4 minutes, 400 mg/m²; IV infusion over 46 hours, 2400 mg/m²; Every 14 days, Until disease progression/toxicity
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Intervention Description
Leucovorin: IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Time Frame
up to 56 days
Secondary Outcome Measure Information:
Title
Adverse Events (NCI-CTC 4.0)
Time Frame
28 days after the last dose
Title
Plasma pharmacokinetics (PK) parameters for Sevacizumab
Time Frame
Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8 ,Day11)
Title
Plasma pharmacokinetics (PK) parameters (Cmax, Tmax, AUC, T1/2) for Irinotecan and its major metabolite SN-38
Time Frame
Day1, Day2, Day3, Day15, Day16, Day17
Title
Plasma pharmacokinetics (PK) parameters for 5-FU
Time Frame
Day1, Day3, Day15, Day17
Title
Potential biomarkers, including VEGF and ADA
Time Frame
VEGF:Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8, Day11); ADA : within 15 minutes before each Sevacizumab administration
Title
Objective Response Rate (ORR)
Time Frame
up to 3 years from date of registration
Title
Disease Control Rate (DCR)
Time Frame
up to 3 years from date of registration
Title
Progression Free Survival (PFS)
Time Frame
up to 3 years from date of registration
Title
Overall Survival (OS)
Time Frame
up to 3 years from date of registration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histological/cytological confirmed unresectable metastatic colorectal cancer patients who have failed first-line oxaliplatin-based chemotherapy
At least one measurable lesion (according to RECIST 1.1 )
At least 4 weeks from the last chemotherapy. If patients received anti-tumor biological products, at least four t1/2 of washout period is needed
Toxicity from previous treatment has to restore to ≤ grade 1 (NCI CTC4.0)
ECOG performance status 0-1
Life expectancy ≥ 3 months
Adequate hematologic function: ANC ≥ 1.5 × 10^9 /L, HB ≥ 90 g /L (blood transfusion allowed), PLT ≥ 100 ×10^9 /L; Adequate hepatic function: ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN (patients with liver metastases ALT ≤ 5 × ULN, AST ≤ 5 × ULN); Adequate renal function: creatinine ≤ 1 × ULN; Coagulation function: INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN
Patients of childbearing potential (male and female) must agree to use reliable methods of contraception until at least 12 weeks after the last dose
Patients signed written inform consent
Willingness and capability to communicate with investigators and to comply with protocol requirements
Exclusion Criteria:
HCV, TP or HIV antibody positive
Previously received anti-VEGF protein drugs, such as Bevacizumab,Sevacizumab
Previously treated with irinotecan
History of dihydropyrimidine dehydrogenase deficiency
Patients with alcohol or drug dependence
Participation in other clinical trials within 4 weeks before enrollment
Active or chronic hepatitis B infection with HBV DNA > 1.0 * 10^3 IU/mL
Serious infection requiring intravenous antibiotic therapy
Symptomatic brain metastases
Patients with proteinuria at screening (urine protein ≥ 1+)
History of abdominal fistula, gastrointestinal perforation, abdominal abscess within 6 months prior to enrollment
History of intestinal obstruction, inflammatory bowel disease, or other intestinal diseases with chronic diarrhea as the major symptom
Serious non-healing wounds, ulcers or fractures
Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to enrollment
Active bleeding within 3 months prior to enrollment
Bleeding diathesis or coagulation disorder
History of arterial or venous thrombosis
History of myocardial infarction or stroke within 6 months prior to enrollment
Unstable angina, congestive heart failure, New York Heart Association (NYHA) class II heart failure, uncontrollable arrhythmia, uncontrolled hypertension
Expected to receive surgery during the study or within 1 month after the last dose
The investigators consider the patients are not suitable for this trial
Pregnant and lactating women
Known allergies to any excipient in the study drug
Patients can not complete this study for any other reason
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Haijun Li, MS
Phone
86-025-85560000
Ext
1625
Email
lihaijun@simcere.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin Li, MD
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Bethune Hospital of Jilin University
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yanhua Ding
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jin Li
Facility Name
The First Hospital of Zhejiang Province
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nong Xu
12. IPD Sharing Statement
Learn more about this trial
A Phase Ib Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer
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